Sara E. Cruz-Morales

The distribution of fos immunoreactivity in rat brain following freezing and escape responses elicited by electrical stimulation of the inferior colliculus

Several sources of evidence indicate that the inferior colliculus also integrates acoustic information of an aversive nature besides its well-known role as a relay station for auditory pathways. Gradual increases of the electrical stimulation of this structure cause in a hierarchical manner alertness, freezing and escape behaviors. Independent groups of animals implanted with bipolar electrodes into the inferior colliculus received electrical stimulation at one of these aversive thresholds. Control animals were submitted to the same procedure but no current was applied. Next, analysis of Fos protein expression was used to map brain areas activated by the inferior colliculus stimulation at each aversive threshold and in the controls. Whereas alertness elicited by stimulation of the inferior colliculus did not cause any significant labeling in any structure studied in relation to the respective control, electrical stimulation applied at the freezing threshold increased Fos-like immunoreactivity in the central amygdaloid nucleus and entorhinal cortex. In contrast, escape response enhanced Fos-like immunoreactivity in the nucleus cuneiform and the dorsal periaqueductal gray matter of the mesencephalon. This evidence supports the notion that freezing and escape behaviors induced by electrical stimulation of the inferior colliculus activate different neural circuitries in the brain. Both defensive behaviors caused significant expression of c-fos in the frontal cortex, hippocampus and basolateral amygdaloid nucleus. This indistinct pattern of c-fos distribution may indicate a more general role for these structures in the modulation of fear-related behaviors. Therefore, the present data bring support to the notion that amygdala, dorsal hippocampus, entorhinal cortex, frontal cortex, dorsal periaqueductal gray matter and cuneiform nucleus altogether play a role in the integration of aversive states generated at the level of the inferior colliculus.

Sex differences in serotonergic activity in dorsal and median raphe nucleus.

There is evidence on the existence of sex differences in the serotonergic system of the raphe. This study examines sex-based differences in serotonergic activity in the dorsal (DRN) and median (MRN) raphe nucleus; two structures that have consistently been implicated in the brain circuitry associated with fear and anxiety reactions. We also analyzed the effects of the elevated plus-maze (EPM) test, which allows the measuring of behavioral reactions to stress on rats produced by fear to height and open spaces on such sex differences. The present study was carried out on 70- to 80-day-old rats exposed or not to the EPM test. Immediately after the test, or 10-12 days later, groups of animals were sacrificed to measure serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) concentration in the DRN and MRN, to calculate the serotonergic activity ([5-HIAA]/[5-HT]). Serotonergic activity in the females DRN was consistently higher than in males DRN. Such differences were not observed in the MRN. While exposed to the EPM test, female rats display more aversive responses than males, only during the day of diestrus 1. After the EPM test, serotonergic activity decreased in the females DRN and in the males MRN, both immediately and 10-12 days later. The sex-based differences in fear/anxiety reported in this study could be linked to the observed decrease in serotonergic activity in the DRN of female rats after the EPM test.

Is acetylcholine involved in memory consolidation of over-reinforced learning?

Systemic administration of anticholinergic drugs produces amnesia. To determine whether this effect can be prevented by increasing the magnitude of the learning experience, independent groups of rats were trained in passive avoidance, using a 3.0-mA footshock, and then injected with scopolamine (2, 4, 6, 8 or 12 mg/kg). When retention of the task was evaluated, a dose-dependent amnesic effect was found. When footshock intensity was increased to 6.0 and 9.0 mA, injections of 8 and 12 mg/kg of scopolamine did not produce memory impairments. These findings indicate that acetylcholine plays an important role in consolidation of passive avoidance, but it does not seem to be involved in memory processes when the magnitude of the negative reinforcer is increased.

Differential effects of cholinergic blockade of anterior and posterior caudate nucleus on avoidance behaviors

Groups of rats were trained in a one-trial passive avoidance task and then tested for retention 24 and 48 h later. They were also trained, in a single session, according to a one-way active avoidance paradigm. The effects of microinjections of atropine or of saline into the anterior caudate nucleus (CN) and of atropine into the posterior CN were assessed on these conditioned responses. Only those rats injected with atropine in the anterior CN showed a retention deficit in passive avoidance, while no effects on active avoidance became evident in any of the groups. These results suggest that cholinergic activity of the anterior CN is critically involved in memory consolidation of passive avoidance, but not in the processes mediating the acquisition of relatively simple active avoidance learning.

A threshold for the protective effect of over-reinforced passive avoidance against scopolamine-induced amnesia.

Acetylcholine-receptor blockers produce amnesia of aversively motivated behaviors. However, when animals are submitted to relatively high intensities of footshock (over-reinforcement), anticholinergic treatment does not induce memory impairments. The aim of this work was to determine whether the antiamnesic effect produced by increasing the magnitude of the negative reinforcer is gradually established or if a threshold should be reached to obtain such an effect. Wistar rats were trained in passive avoidance using 2.5, 2.6, 2.7, 2.8, 2.9 or 3.0 mA; 5 min after training they were given one systemic injection of scopolamine (8 mg/kg). An amnesic state was produced in the groups that were trained with the lower intensities (2.5-2.7 mA); with the three higher intensities near-perfect retention was evident. These results suggest that acetylcholine is critically involved in memory consolidation, and that by increasing the magnitude of the negative reinforcer, a threshold is reached where cholinergic activity of the nervous system is not necessary for the development of the consolidation process.

Effects of central muscarinic blockade on passive avoidance: Anterograde amnesia, state dependency, or both?

It was recently reported that administration of relatively high intensities of footshock (overreinforcement) during training of passive avoidance protected animals against the amnesic effect of scopolamine, injected 5 min after training. This was interpreted in terms of a lesser involvement of acetylcholine in memory consolidation. An alternative explanation was that overreinforcement accelerated the consolidation process, which could have taken place before the injection of scopolamine. To test for this possibility, male Wistar rats were injected with 4, 8, or 12 mg/kg of scopolamine, 5 min before training with low or high levels of footshock and then tested for retention of the task. Scopolamine induced the expected memory deficit after the low-intensity footshock; after overreinforcement the higher doses of scopolamine induced state dependency, while no deficits were produced with the lower dose. It was concluded that: (a) acetylcholine is indeed involved in memory consolidation of passive avoidance; (b) scopolamine interacts with high footshock levels to produce state dependency; and (c) when relatively low doses of scopolamine are used in conditions of overreinforcement, protection against scopolamine-induced amnesia becomes evident.

Time-dependent effects of cholinergic blockade of the striatum on memory

Rats were trained on a passive avoidance task, and a retention test was carried out 24 h later. Scopolamine was injected into the anterior striatum at one of various intervals following training: at 2 min it produced amnesia; an intermediate degree of impairment was found when given 8 min after training. With a delay of 15 min, this drug did not produce an interference with memory. These observations suggest that striatal cholinergic activity is involved in memory consolidation.

Characterization of a xylose containing oligosaccharide, an inhibitor of multidrug resistance in Staphylococcus aureus, from Ipomoea pes-caprae.

Pescaprein XVIII (1), a type of bacterial efflux pump inhibitor, was obtained from the CHCl(3)-soluble resin glycosides of beach morning glory (Ipomoea pes-caprae). The glycosidation sequence for pescaproside C, the glycosidic acid core of the lipophilic macrolactone 1 containing D-xylose and L-rhamnose, was characterized by means of several NMR techniques and FAB mass spectrometry. Recycling HPLC also yielded eight non-cytotoxic bacterial resistance modifiers, the two pescapreins XIX (2) and XX (3) as well as the known murucoidin VI (4), pecapreins II (6) and III (7), and stoloniferins III (5), IX (8) and X (9), all of which contain simonic acid B as their oligosaccharide core. Compounds 1-9 were tested for in vitro antibacterial and resistance-modifying activity against strains of Staphylococcus aureus possessing multidrug resistance efflux mechanisms. All of the pescapreins potentiated the action of norfloxacin against the NorA over-expressing strain by 4-fold (8 microg/mL from 32 microg/mL) at a concentration of 25 microg/mL.

The Ovarian Innervation Participates in the Regulation of Ovarian Functions

The release of gonadotropins is the main endocrine signal regulating ovulation and the release of hormones by the ovaries. Several types of growth factors modulate the effects of gonadotropins on the follicular, luteal and interstitial compartments of the ovaries. During the last 30 years, numerous studies have indicated that the ovarian innervations play a role in modulating the effects that gonadotropin have on the ovaries’ ability to ovulate and secrete steroid hormones. This literature review presents a summary of the experimental results obtained by analyzing the effects of stimulating or blocking the well-known neural pathways participating in the regulation of ovulation and secretion of steroid hormones. Together, the results suggest that various neurotransmitter systems modulate the effects of gonadotropins on ovulation and the ovaries capacity to secrete steroid hormones. In addition, the ovaries asymmetric capacity for ovulation and hormone secretion could be explained by the asymmetries in their innervations.

Acute restriction impairs memory in the elevated T-maze (ETM) and modifies serotonergic activity in the dorsolateral striatum

Serotonin (5-HT) is involved in behaviors such as sleep, eating, memory, in mental disorders like anxiety and depression and plays an important role in the modulation of stress. On the other hand, exposure to stress influence learning as well as declarative and non-declarative memory. These effects are dependent on the type of stressor, their magnitude, and the type of memory. The striatum has been associated with non-declarative procedural memory, while the information about stress effects on procedural memory and their relation with striatal serotonin is scarce. The objective of this study was to evaluate the effects of stress on the modifications of the striatal serotonergic system. In Experiment 1, the effects of either 60 min of restraint (R) or exposure to the elevated T-maze (ETM) was assessed. Exposure to ETM decreased 5-HT concentration and to R increased 5-HT activity ([metabolite]/[neurotransmitter]). In Experiment 2, we evaluated the effects of restraint on ETM trained immediately, 24 or 48 h after restraint. No effects were detected in acquisition or escape latencies, while retention latencies were lower in all groups compared with the non-restrained group, although significant effects were detected immediately and 24h after restraint. The memory impairment seems to be associated with changes in striatal serotonergic system, given that 5-HT concentration increased, while serotonergic activity decreased. The differences in the activity of 5-HT detected in each experiment could be explained by the effects of different stressors on the serotonergic neurons ability to synthesize the neurotransmitter. Thus, we suggest that exposure to stress impairs procedural memory and that striatal serotonin modulates this effect.